BothAlzheimer'sdisease(AD)anddepressionhavebecomeincreasinglymoreprevalentin thehomeboundelderly,leadingtoincreasedratesofmorbidity,nursinghomeplacementand mortality,thanwhatarefoundinthegeneralelderlypopulation.Ourcross!sectionalstudyofan establishedhomeboundpopulationintheBostonareahasfoundthatlowplasmaamyloid!b42 (Ab42)isassociatedwithdepressionindependentlyofcardiovasculardisease.Wefurther foundthatdepressionwithlowAb42combinedwithhighAb40inplasmaisassociatedwith poormemory.SimilarlyotherresearchstudieshaveshownthatahighplasmaA40/A42 ratiosignificantlyincreasedtheriskofAD.MultiplestudiesdemonstratethatplasmaA correlateswithcerebralspinalfluid(CSF)Awhencognitionisnormal,butthisequilibrium disappearsaftertheADcognitivesymptomsoccur.Wehypothesizetheexistenceofa potentialdepressionsubtypeassociatedwithAbpeptidesinplasma,whichwehavetermed amyloid!associateddepression.ThepurposeofthisR01applicationistovalidatethe existenceofamyloid!associateddepressiondefinedbyahighplasmaA40/A42ratio,andto investigatewhetherthisdepressionsubtypeisaprodromaldepressionofAD.Theproposalis basedonourestablishedpopulation,andhastwoaims:Aim1istodocumentmemorydecline prospectivelyinthosewithamyloid!associateddepressionvs.thosewithnon!amyloid depressionvs.thecontrols.Aim2istoinvestigatetherelationshipbetweenplasmaAand CSFA,acentralnervoussystem(CNS)biomarkerofAD,inthedifferentdepression subgroups.Ourlong!termgoalistoidentifyprodromalsignsofADtohelpfacilitateearly treatmentofthediseaseinthehomeboundelderlypopulation.